54 non-anemic young women (aged 12-49y) with plasma ferritin ≤20 µg/L were recruited and subsets of 13-25 individuals were given labeled iron (FeSO4) at different single doses orally on 1 or on 2 consecutive days, or three 60-mg Fe doses (twice-daily dosing) within 24 hours.

In the single dose administration, 24 hours after doses ≥60 mg, serum hepcidin was increased and the fraction of the iron being absorbed was decreased by 35% to 45%. With increasing dose, fractional absorption decreased whereas absolute absorption increased. Total iron absorbed from 3 doses (2 mornings and an afternoon) was not significantly greater than that from 2 morning doses. Providing lower dosages (40-80 mg Fe) and avoiding twice-daily dosing maximized fractional absorption. The duration of the hepcidin response supported alternate day supplementation.

*Current dosing recommendations giving iron multiple times a day seem to reduce the iron absorption of subsequent doses by increasing hepcidin with negative feedback on iron absorption from the guts.